A primary objective of obesity research is to define the pathophysiology of obesity as a basis for preventing and/or effectively treating the disease. The areas for research involving bariatric surgery patients may include: 1) defining optimal surgical approaches, 2) identification of biological and genetic differences that influence development of comorbidities and outcomes of surgery, and 3) utilizing this population as a model for study of the pathogenesis and response to treatment of obesity. We propose that the Bariatric Research Clinical Research Consortium (BSCRC) employ a comprehensive relational database that includes parameters readily available to all Clinical Centers (CCs), such as basic anthropometrics, measures of body composition, clinical and surgical history, and recording of a quantitative comorbidity scale. This scale scores each of 17 comorbidities related to obesity, including diabetes, hypertension, and hyperlipidemia, and utilizes treatment as a gauge for the severity of symptoms. Further refinement to the comorbidity scale grading may be required by BSCRC participants. This scale will enable comorbidities to be correlated with mRNA expression profiles and endocrine response. UC Davis proposes two specific protocols for conduct by the BSCRC. The short term protocol will measure, using quantitative PCR, the mRNA expression level of obesity related genes in the subcutaneous and omental fat, liver, and intestine of bariatric surgery patients at the time of operation. Measures of body composition including the distribution of body fat, endocrine response to gastric bypass, and the clinical comorbidity scores will allow detailed phenotyping of the subjects from the time of operation to timepoints 2 years post-op. This will be an important initial step towards understanding the variation of comorbidity occurrence between subjects of similar adiposity. The longer term protocol will be a 3-5 year longitudinal study of the response to gastric bypass in relation to hormone activity, body composition, and physical activity. At this phase, correlation with the preoperative genetic and endocrine markers derived in the short term study, as well as history of comorbidity scores, would identify those patients who would most benefit from gastric bypass. This and other data accumulated by the BSCRC will provide a basis for establishment of further studies of obesity comorbidities and their response to surgical treatment.